Changes in subchondral bone morphology with osteoarthritis in the ankle

Abstract

Significant alterations to subchondral trabecular bone microarchitecture are observed in late-stage osteoarthritis (OA). However, detailed investigation of these changes to bone in the ankle are under-reported. This study aimed to fully characterise the trabecular morphology in OA ankle bone specimens compared to non-diseased (ND) controls using both standard and individual-trabecular segmentation-based (ITS) analyses. Ten ND tibial bone specimens were extracted from three cadaveric ankles, as well as five OA bone specimens from patients undergoing total ankle arthroplasty surgery. Each specimen was scanned using microcomputed tomography from which a 4 mm cuboidal volume was extracted for analysis. Morphological parameters for the subchondral trabecular bone were measured using BoneJ (NIH ImageJ) and 3D ITS for whole volumes and at each depth level in 1 mm increments. The results show an overall increase in bone volume fraction (p<0.01) and trabecular thickness (p<0.001) with OA, with a decrease in anisotropy (p<0.05). ITS analysis showed OA bone was composed of more rod-like trabeculae and plate-like trabeculae compared to ND bone. Numerous properties were depth dependent, but the results demonstrated that towards the subchondral bone plate, both rod- and plate-like trabeculae were thicker, rods were longer and plates had increased surface area. Overall, this study has verified key microstructural alterations to ankle subchondral bone that are found in other OA lower-limb joints. Depth-based analysis has highlighted differences of interest for further evaluation into the remodelling mechanisms that occur with OA, which is critical to understanding the role of subchondral bone microarchitecture in the progression of the disease.

Fig 1. Location of an exemplary set of late-stage osteoarthritic ankle bone samples obtained from patient undergoing total ankle arthroplasty.

Fig 2. Study workflow showing exemplary cuboidal portions of ND and OA bone taken from μCT image data for full morphological evaluation.

The volumes were also split into four 1 mm levels to evaluate the sensitivity of each morphological property to increasing depth from the subchondral bone plate.

Fig 3. Distribution of standard morphological values for OA vs. ND groups of distal tibial specimens.

The box plots represent the median and interquartile range of values for N = 5 OA specimens and N = 10 ND specimens. Significance levels are indicated using: *p<0.05, ** p<0.01, *** p<0.001, ns = non-significance.

Fig 4

A comparison between ND (a) and OA (e) exemplary specimen subvolumes (2 mm). EF results show EF >0 (yellow-orange, f) or more rod-like trabeculae in the OA specimens. In comparison, ND specimens show EF <0 (purple-blue, b) indicating more plate-like trabeculae. Finn peak plots (c,g) show shift to of distribution toward the bottom-right for plate-dominated geometry (c) and top-left for rod-dominated geometry (g). Histograms and summary statistics (d,h) further demonstrate the shift in values towards either +1 (h; rod-dominated geometry) or -1 (d; plate-dominated geometry). The box plots (i, j represent the median and interquartile range of EF and SMI values for (N = 5) OA specimens and (N = 10) ND whole cuboidal specimens. Significance levels are indicated using: * p<0.05, ns = non-significance.

Fig 5. Distribution of ITS-based morphological values for OA vs. ND groups for specimens from the distal tibia.

Two exemplary volumes show the increasing in rod-like trabeculae (orange) compared to plate-like trabeculae (blue) in OA specimens. The box plots represent the median and interquartile range of values for OA specimens (N = 5) and ND specimens (N = 10). Levels of significance indicated using: * p<0.05, ** p<0.01, *** p<0.001, ns = no significance.

Fig 6. Comparison of AVG (bars) ± SD (error bars) standard morphological properties with increasing depth from the SBP for OA and ND specimens, grouped by level.

Levels of significance indicated using: * p<0.05, ** p<0.01, *** p<0.001, ns = no significance.

Fig 7. Comparison of AVG (bars) ± SD (error bars) 3D ITS-based morphological properties with increasing depth from the SBP grouped by level (pBV/TV, rBV/TV, rTb.Th, pTb.Th, pTb.S, rTb.l) and showing intra-level variation in properties (pTb.S).

Levels of significance indicated using: * p<0.05, ** p<0.01, *** p<0.001, ns = no significance.